Natural Product: NPC259070

Natural Product IDNPC259070
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NOXWYBLOGTVDPC-GGJBVRJYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 23928115
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0000507] Isoflavonoid O-glycosides

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey NOXWYBLOGTVDPC-GGJBVRJYSA-N
Standard InCHI InChI=1S/C22H22O9/c1-10-18(24)20(26)21(27)22(30-10)31-17-8-15-13(7-16(17)28-2)19(25)14(9-29-15)11-3-5-12(23)6-4-11/h3-10,18,20-24,26-27H,1-2H3/t10-,18-,20+,21+,22-/m0/s1
SMILES C[C@H]1[C@@H]([C@H]([C@H]([C@@H](O1)Oc1cc2c(cc1OC)c(=O)c(co2)c1ccc(cc1)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   430.13 Volume:   412.863
?
Van der Waals volume.
Dense:   1.042 LogP:   0.811
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.301
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.453
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   24.0
TPSA:   138.82
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   4.0 Rings:   4.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.483 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.72 Fsp3:   0.318
MCE-18:   83.621
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.532 Fluc inhibitor:   0.316
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.912
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.561
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.127 Promiscuous compounds:   0.504

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.956 MDCK Permeability:   -5.168
Pgp-inhibitor:   0.004 Pgp-substrate:   0.588
PAMPA:   0.997
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.151
20% Bioavailability (F20%):   0.329 30% Bioavailability (F30%):   0.325
50% Bioavailability (F50%):   0.948

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.392
Plasma Protein Binding (PPB):   84.792% Volume Distribution (VD):   -0.045
Fu: 16.937%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.966
OATP1B3 inhibitor:   0.974 BCRP inhibitor:   0.255
BSEP inhibitor:   0.562

ADMET: Metabolism

CYP1A2-inhibitor:   0.018 CYP1A2-substrate:   0.206
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.128
CYP2C9-inhibitor:   0.445 CYP2C9-substrate:   0.084
CYP2D6-inhibitor:   0.009 CYP2D6-substrate:   0.002
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.996
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.997
HLM stability:   0.011
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  3.199 Half-life (T1/2):  3.114

ADMET: Toxicity

hERG Blockers:  0.1 hERG Blockers (10um):  0.463
Human Hepatotoxicity (H-HT):  0.518 Drug-induced Liver Injury (DILI):  0.747
AMES Toxicity:  0.662 Rat Oral Acute Toxicity:  0.113
Maximum Recommended Daily Dose:  0.219 Skin Sensitization:  0.685
Carcinogencity:  0.247 Eye Corrosion:  0.0
Eye Irritation:  0.486 Respiratory Toxicity:  0.059
Drug-induced Neurotoxicity:  0.054 Ototoxicity:  0.802
Hematotoxicity:  0.146 Drug-induced Nephrotoxicity:  0.44
Genotoxicity:  0.61 RPMI-8226 Immunitoxicity:  0.114
A549 Cytotoxicity:  0.138 Hek293 Cytotoxicity:  0.352
BCF:   0.797
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   3.501
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.706
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.153
?
96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO40231 Streptomyces sp. RB1 Strain Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[28006913]
NPO40231 Streptomyces sp. RB1 Strain Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1173 Organism Candida albicans SC5314 Candida albicans SC5314 MIC > 100.0 ug.mL-1 PMID[28006913]
NPT85 Organism Filobasidiella neoformans Cryptococcus neoformans MIC > 100.0 ug.mL-1 PMID[28006913]
NPT19 Organism Escherichia coli Escherichia coli MIC > 100.0 ug.mL-1 PMID[28006913]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 100.0 ug.mL-1 PMID[28006913]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC259070 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.8429 Intermediate Similarity NPC105511
0.7778 Intermediate Similarity NPC211014
0.7067 Intermediate Similarity NPC348541
0.6933 Remote Similarity NPC135345
0.6769 Remote Similarity NPC605229
0.6582 Remote Similarity NPC205076
0.6538 Remote Similarity NPC161749
0.6533 Remote Similarity NPC25547
0.6173 Remote Similarity NPC100720
0.6076 Remote Similarity NPC160515
0.5926 Remote Similarity NPC197896
0.5926 Remote Similarity NPC313163
0.5909 Remote Similarity NPC303913
0.5679 Remote Similarity NPC45165
0.5568 Remote Similarity NPC487212
0.5542 Remote Similarity NPC258035
0.5517 Remote Similarity NPC48773
0.5465 Remote Similarity NPC229729
0.5417 Remote Similarity NPC181124
0.5417 Remote Similarity NPC100971
0.5385 Remote Similarity NPC475155
0.5294 Remote Similarity NPC73511
0.5227 Remote Similarity NPC307518
0.5217 Remote Similarity NPC479405
0.5208 Remote Similarity NPC231194
0.5205 Remote Similarity NPC216769
0.5172 Remote Similarity NPC481043
0.5172 Remote Similarity NPC224462
0.5169 Remote Similarity NPC479407
0.5161 Remote Similarity NPC479404
0.5143 Remote Similarity NPC120924
0.5135 Remote Similarity NPC487217
0.5119 Remote Similarity NPC331652
0.5116 Remote Similarity NPC46420
0.5056 Remote Similarity NPC479406

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC259070 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
0.6538 Remote Similarity NPD4381 Clinical (unspecified phase)
0.5301 Remote Similarity NPD3818 Discontinued

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data